The goal of this Program Project is to integrate advances in cancer biology and optical technology to develop cost-effective tools to aid in early detection of cervical cancer. Cervical cancer is the second most common cancer among women worldwide, and the leading cause of cancer death in women in developing countries. Our team of scientists, engineers, clinicians, and social scientists is developing optical tools to monitor biologically predictive features of cervical cancer. In this Program Project, we have demonstrated that quantitative imaging and analysis of cytologic smears and histopathologic specimens can improve screening and diagnosis of cervical cancer and its precursors. This automated approach can substantially reduce the need for clinical expertise;the shortage of adequately trained health care personnel is a critical obstacle which prevents screening in many low-resource settings. Project 1 is devoted to developing a biological model of cervical neoplasia. This integrated model will guide the invention, assessment, and improvement of new optical technologies for the screening and diagnosis of cervical cancer. Using our rich database of quantitative histopathology images of the cervix, the models will depict the 3D structure of the cervix at the microscopic level. The model will also describe spatial changes in cellular and nuclear morphology, tissue architecture, ploidy, inflammation, angiogenesis and biomarker expression throughout the epithelium and stroma of each pathologically defined phase of cervical neoplasia. We will incorporate electromagnetic models to describe relationships between light reflectance behavior and tissue properties. After carefully validating the model in a series of 2D and 3D imaging experiments, we will use the model to guide the development of new cancer imaging devices. Because HPV vaccines could take decades to deploy, early detection remains our best defense against cervical cancer. We also hope that the models derived in this Project can be applied in the future to aid in the development of diagnostic equipment to prevent or guide the treatment of other diseases.